The long-term goal of this AREA proposal is to understand the relationship between body fat and fertility. The experimental model selected for this study is the heterozygous (Ay/-) female mouse of the C57BL/6J strain which exhibits decreased immunocompetence, obesity and loss of fertility at a relatively early age (approx. 200 days). The working hypothesis is that one or more of the hormones from the hypothalamo-pituitary-ovarian axis may be inadequate thus upsetting the intricate feedback interactions in the hypothalamo-pituitary-ovarian axis resulting in decreased fertility. The specific aims of this project are to test mating success, ovulatory rates and serum levels of LH, FSH, PRL, estrogens and progesterone in the heterozygous yellow and age-matched a/a black controls at various ages (young, pre-obese and aging obese). Mice will be sacrificed at 150, 180, 210 and 240 days of age during various stages of the estrous cycle (assessed by vaginal smears) and during pregnancy. Since enough serum is obtained from one mouse to measure only one hormone, these studies will be conducted in stages for each of the hormones. Preliminary work has been initiated with FSH analysis and mating/ovulatory rates. Additionally, the effects of high fat (11 percent) and fat restricted (4 percent) diets will be compared to determine whether the high fat diet accelerates obesity and loss of fertility and to assess its effects on hormonal secretions of the hypothalamo-pituitary-ovarian axis. To identify the site of hormonal abnormalities (pituitary versus hypothalamus) in the obese mice, the gonadotropins response to ovariectomy and to exogenous administration of GnRH will be studied. The contribution of body fat to blood estrone levels leading to chronically elevated estrogens in the obese mice will be determined by calculating the ratio of total estrogens to estradiol. Hormones will be analyzed by RIA. The LH and FSH RIA are established, however, the steroid assays have yet to be set up. Status of PRL RIA is not stated.